Authors
Raphaël Mattiuz, Jesse Boumelha, Emmanouil Aerakis, Jessica Le Berichel, Pauline Hamon, Laszlo Halasz, Abishek Vaidya, Brian Y Soong, Emir Radkevich, Hye Mi Kim, Matthew D Park, Romain Donne, Leanna Troncoso, Rachel A Kaplan, Clotilde Hennequin, Isaias Hernández-Verdin, Lucía López, Frederika Rentzeperis, Darwin D'Souza, Medard Ernest Kaiza, Ian P MacFawn, Meriem Belabed, Guillaume Mestrallet, Etienne Humblin, Raphaël Merand, Samarth Hegde, Jean-Christophe Lone, Giorgio Ioannou, Sinem Ozbey, Igor Figueiredo, Alexander Tepper, Hajer Merarda, Nadine Serhan, Maximilian M Schaefer, Jinping An, Ray A Ohara, Erika Nemeth, Simon Goldstein, Amanda M Reid, Moataz Noureddine, Alexandra Tabachnikova, Giulia Maria Piperno, Maria Tsoumakidou, Jalal Ahmed, Alexandros D Polydorides, Nina Bhardwaj, Amaia Lujambio, Zhihong Chen, Edgar Gonzalez Kozlova, Seunghee Kim-Schulze, Joshua D Brody, Michael Schotsaert, Christine Moussion, Sacha Gnjatic, Vladimir Roudko, Florent Ginhoux, Kenneth M Murphy, Catherine Sautès-Fridman, Wolf Herman Fridman, Brian D Brown, Thomas U Marron, Federica Benvenuti, Jason G Cyster, Hélène Salmon, Tullia C Bruno, Nikhil S Joshi, Alice O Kamphorst, Miriam Merad
Published in
Science (New York, N.Y.). Volume 393. Issue 6808. Pages eady1678. Jul 16, 2026. Epub Jul 16, 2026.
Abstract
Tertiary lymphoid structures (TLSs) are associated with immunotherapy response, yet the mechanisms controlling their formation and maintenance remain unclear. Using spatial transcriptomics and multiplex imaging across human tumors, we found that CCR7+ mature dendritic cells (DCs) accumulate in TLSs. In a mouse non-small cell lung cancer model that forms mature TLSs, we show that early TLS development requires interferon-γ (IFN-γ)-driven type 1 conventional dendritic cell (cDC1) maturation, migration to tumor-draining lymph nodes (tdLNs), and T cell recruitment. As tumors progress, TLSs persist independently of tdLN T cell egress, coinciding with cDC1 accumulation within intratumoral CCL19 stromal hubs. There, cDC1-major histocompatibility complex class 1 (MHC-I) and -MHC-II concomitant antigen presentation, along with CD40 signaling, sustain TLS, T follicular helper (TFH) cell pool, germinal centers, and tumor-specific immunoglobulin G (IgG). These findings highlight local mature cDC1s as key TLS orchestrators and potential targets to enhance antitumor TLS function.
PMID:
42462020
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.
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